Trifluoromethanesulfonic anhydride → HCID 90735055, 화합물

HRID 502926노트

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HRID 502926 반응식
[C:1]([C:3]1[CH:4]=[C:5]([S:9]([N:12]2[CH2:16][C@@H:15](O)[CH2:14][C@H:13]2[C:18]([O:20][CH3:21])=[O:19])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1)#[N:2].C(N(C(C)C)CC)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.Cl.[F:47][C:48]1([F:54])[CH2:53][CH2:52][CH2:51][NH:50][CH2:49]1>C(Cl)Cl>[C:1]([C:3]1[CH:4]=[C:5]([S:9]([N:12]2[CH2:16][C@H:15]([N:50]3[CH2:51][CH2:52][CH2:53][C:48]([F:54])([F:47])[CH2:49]3)[CH2:14][C@H:13]2[C:18]([O:20][CH3:21])=[O:19])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1)#[N:2]

참가 물질

6

반응물 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531Diisopropylethylamine2회HCID 27583493,3-Difluoropiperidine hydrochlorideHCID 57629160HCID 57629160, 화합물

생성물 1

HCID 90735055HCID 90735055, 화합물

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of the compound of Step 1 (19.6 g, 63.2 mmol), diisopropylethylamine (16.5 g, 127 mmol), and CH2Cl2 (200 mL) was added trifluoromethanesulfonic anhydride (17.8 g, 63.2 mmol) via syringe pump at −60° C. over 30 minutes. The resulting solution was then warmed to −20° C. over 1.5 h, whereupon diisopropylethylamine (5.5 g, 42.5 mmol) was added followed by 3,3-difluoropiperidine hydrochloride (6.67 g, 42.5 mmol). The mixture was then slowly warmed to rt over 5 h. After 12 h at rt, the reaction was partitioned between H2O (150 mL) and CH2Cl2 (100 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (3×100 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated. The residue was purified on silica gel (1:99→99:1 ethyl acetate-hexanes) to afford the title compound as a colorless foam: 1H NMR (500 MHz, CDCl3) δ 8.16 (s, 1H), 8.10 (d, 1H), 7.88 (d, 1H), 7.68 (t, 1H), 4.48-4.59 (m, 1H), 3.73 (s, 3H), 3.68-3.65 (m, 1H), 3.22-3.17 (m, 2H), 2.64 (br q, 1H), 2.51 (br q, 1H), 2.42-2.41 (m, 2H), 2.23-2.20 (m, 1H), 2.13-2.04 (m, 1H), 1.90-1.82 (m, 2H), 1.74-1.72 (m, 2H); LRMS (ESI) m/z 414 (414 calcd for C18H21F2N3O4S, M+H).

후처리

  1. additionwas added
  2. customthe reaction was partitioned between H2O (150 mL) and CH2Cl2 (100 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (3×100 mL)
  5. dry with materialThe combined organic layers were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel (1:99→99:1 ethyl acetate-hexanes)

출처 및 근거

ORD 기록
ord-dbaef7be04344451b2041a95aba812ef
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07776891B2

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